UNIPROT:P50583 - FACTA Search

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We used light and electron microscope immunocytochemistry to compare the development of the pattern of innervation and synaptic organization of the serotonin (5-HT) afferent system in sensory (visual and somatosensory) and motor areas of the rat cerebral cortex. Serotonin-labeled fibers were present in all cortical areas at birth appearing as two tangential streams, one above and one below the cortical plate. These fibers gradually arborized sending branches into all cortical layers in an "inside-out" sequence that broadly paralleled the gradient of neurogenesis and differentiation in the cortex. A striking feature at the early stages of postnatal development of the visual and somatosensory cortex was the transient presence of a dense accumulation of 5-HT fibers in layer IV. In agreement with earlier reports, transient aggregations of serotonergic axons characterized sensory but not motor areas of the cortex. The innervation pattern characteristic of the adult cortex was attained by the end of the 3rd postnatal week. Electron microscopic analysis of the developing visual cortex showed that 5-HT-containing axonal varicosities formed synaptic contacts, predominantly of the asymmetrical variety, throughout postnatal life. The proportion of varicosities forming synapses increased gradually from birth to reach a peak at the end of the 2nd week, then declined markedly in the subsequent week before rising again at later stages. It appears that the formation of exuberant synapses by 5-HT axons coincides with the period of maturation of the neuronal circuitry of this cortical area. When quantitative analysis was restricted only to layer IV, the proportion of varicosities forming synapses reached a peak at the end of the 1st week of life, when transient innervation was most prominent in this layer. These results suggest that the effects of this dense band of serotonergic axons may be mediated through axodendritic synapses. The types of postsynaptic elements involved in the formation of synapses varied according to age, suggesting progressive morphological differentiation of cortical target neurons or, alternatively, a continuous process of removal and establishment of new connections by 5-HT axons in the visual cortex. In contrast, analysis in the motor cortex revealed a continuous increase in the proportion of 5-HT varicosities engaged in synaptic contacts from birth to the late sages of development. The results presented here provide anatomical evidence for a differential role of 5-HT in the maturation of the cerebral cortex.
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PMID:Regional differences in the ontogeny of the serotonergic projection to the cerebral cortex. 859 86

The central nervous systems of the marine molluscs Pleurobranchaea californica (Opisthobranchia: Notaspidea) and Tritonia diomedea (Opisthobranchia: Nudibranchia) were examined for serotonin-immunoreactive (5-HT-IR) neurons and processes. Bilaterally paired clusters of 5-HT-IR neuron somata were distributed similarly in ganglia of the two species. In the cerebropleural ganglion complex, these were the metacerebral giant neurons (both species), a dorsal anterior cluster (Pleurobranchaea only), a dorsal medial cluster including identified neurons of the escape swimming network (both species), and a dorsal lateral cluster in the cerebropleural ganglion (Pleurobranchaea only). A ventral anterior cluster (both species) adjoined the metacerebral giant somata at the anterior ganglion edge. Pedal ganglia had the greatest number of 5-HT-IR somata, the majority located near the roots of the pedal commissure in both species. Most 5-HT-IR neurons were on the dorsal surface of the pedal ganglia in Pleurobranchaea and were ventral in Tritonia. Neither the buccal ganglion of both species nor the visceral ganglion of Pleurobranchaea had 5-HT-IR somata. Afew asymmetrical 5-HT-IR somata were found in cerebropleural and pedal ganglia in both species, always on the left side. The clustering of 5-HT-IR neurons, their diverse axon pathways, and the known physiologic properties of their identified members are consistent with a loosely organized arousal system of serotonergic neurons whose components can be generally or differentially active in expression of diverse behaviors.
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PMID:Serotonin immunoreactivity in the central nervous system of the marine molluscs Pleurobranchaea californica and Tritonia diomedea. 961

The lateralized effects of ethanol (ETOH) upon behavior and monoamine biochemistry in the lizard, Anolis carolinensis, were examined. Eight adult male anoles consumed solutions of 19% ethanol (ETOH) twice daily over the course of 18 days, while controls consumed water. ETOH decreased the use of the left eye/right hemisphere, but not the right eye/left hemisphere, during territorial aggression (p<0.05). During crossover (i.e., ETOH to water and vice versa) this effect was reversible and replicable. Biochemically, an asymmetry was observed in 5-HT levels in the raphe both in ETOH and controls. ETOH increased levels of serotonin (5-HT; p<0.05), and 5-HIAA/5-HT ratios (p<0.05) in the raphe; serotonin levels in several brain regions correlated with aggressive responses. These results suggest that ETOH boosts 5-HT levels in animals subchronically exposed to ETOH. They further suggest that asymmetry in endogenous 5-HT systems may account for the asymmetrical regulation of aggression generally, and may explain the behavioral effects of ETOH upon lateralized aggression.
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PMID:Lateralized effects of ethanol on aggression and serotonergic systems in Anolis carolinensis. 975 91

Previous work demonstrated that the brains of many reptiles, including the American chameleon Anolis carolinensis (A. carolinensis), are functionally 'split'. Because the left eye in this species projects predominantly to the right hemisphere, and vice versa, inferences about lateralized brain functioning can be made in A. carolinensis by observation of eye use during behavioral encounters. Using this model, past work suggested that territorial aggression in Anolis is under the preferential control of the right hemisphere, and that acute stress or chronic alcohol exposure selectively reduces right hemisphere mediated territorial aggression. In addition, drugs which increase serotonin (5-HT) in the synaptic cleft inhibit aggressive responding in anoles in both hemispheres. The current experiment examined whether or not the administration of the serotonin agonists 8-hydroxy-2-(di-n-propylamine) tetralin (8-OHDPAT), quipazine, or meta-chlorophenylbiguanide (mCPBG) alter territorial aggression in Anolis. Nine adult socially isolated male A. carolinensis underwent a series of behavioral trials during which an antagonistic male was introduced into the cage. Once stable responding was initiated, all subjects were injected in a semi-randomized crossover manner with the following agents, (1) lactated Ringer's, (2) the 5-HT2 agonist quipazine (1.5 mg/kg and 3.0 mg/kg), (3) the 5-HT1 agonist 8-OHDPAT (83 mg/kg), and (4) the 5-HT3 agonist mCPBG (3.0 mg/kg and 9 mg/kg). Twenty minutes post injections, the male intruder was reintroduced into the subject's cage. Several behaviors were recorded, including: (1) the time to the first aggressive response, (2) the number of aggressive episodes mediated by the left eye or right eye, and (3) changes in skin color and posture. Aggressive responding was virtually eliminated in all subjects injected with 8-OHDPAT. On the other hand, one-way ANOVA found that both the 9 mg/kg dose of mCPBG (P=0.007), and the 3.0 mg/kg dose of quipazine (P=0.035), selectively decreased territorial aggression mediated by the left eye/right hemisphere compared to lactated Ringer's controls, but had no effect on aggression mediated by the right eye/left hemisphere. Although 8-OHDPAT inhibited aggression, injected subjects developed phenotypic displays of aggressive coloring/posturing, such as blackening of the eye spot and a raising of the neck crest. These results suggest that aggressive action can be differentiated from phenotypic displays that accompany aggression by a 5-HT1 agonist. They also indicate that there is an asymmetrical effect of 5-HT2/5-HT3 serotonin agonists on hemispheric mediation of aggression in this species.
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PMID:Effects of serotonergic drugs on lateralized aggression and aggressive displays in Anolis carolinensis. 980 42

In order to ascertain if and how age, gender and choice of lethal means influence the seasonal distribution of suicide in Italy, data concerning all suicides registered in Italy from 1984 to 1995 have been analyzed, taking these variables into account. In the age group 14-65 years and over a total of 31771 male suicides (mean yearly rate, 12.6 per 100000) and 11984 female suicides (mean yearly rate, 4.4 per 100000) have been identified in Italy during the study period. Suicides in the younger age ranges, both among males and females, show a less marked asymmetrical seasonal distribution than those in the older age groups. Only suicides committed by violent methods (ICD 953-958) show clear evidence of seasonality, with a peak in spring and a low in late autumn. Suicides committed by non-violent methods (950-952) follow no seasonal trend in either sex. Spectral analysis reveals a circannual rhythm for violent suicides (ICD 953-958) in both genders. For male non-violent suicides (ICD 950-952), a period with a frequency of 0.0833 (12 months) has been identified, but with a polarity opposite to that of male violent suicides. For female non-violent suicides, no period of frequency of 0.0833 could be identified, but, as for female violent suicides, a period with frequency close to 0.2500 (4 months) has been found. Changes in climate, then, correlate with the monthly distribution of violent and non-violent suicides in opposite ways: male violent suicides show a significant positive relationship with indicators of temperature and exposure to the sun, and a significant negative relationship with indicators of humidity and rainfall. Female suicides show less significant relationships with climate indicators. Work aimed at suicide prevention should therefore take into account the complex influence of seasonal climate both on human biological rhythms (particularly on 5-HT related functions and their actions on mood and impulsivity) and on sociorelational habits.
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PMID:Seasonality in suicides: the influence of suicide method, gender and age on suicide distribution in Italy. 985 38

Generally, compounds discriminated by animals possess psychotropic effects in animals and humans. As with many other drugs of abuse, strength of the ethanol discriminative stimulus is dose related. The majority of studies show that doses close to 1.0 g/kg are close to the minimum at which the discrimination can be learned easily. Substitution studies suggest that anxiolytic, sedative, atactic, and myorelaxant effects of ethanol all play an important role in the formation of its intercoeptive stimulus. Low doses of ethanol produce more excitatory cues, similar to amphetamine-like subjective stimuli, whereas higher doses produce rather sedative/hypnotic stimuli similar to those elicited by barbiturates. Substitution studies have shown that the complete substitution for ethanol may be exerted by certain GABA-mimetic drugs acting through different sites within the GABA(A)-benzodiazepine receptor complex (e.g., diazepam, pentobarbital, certain neurosteroids), gamma-hydroxybutyrate, and antagonists of the glutamate NMDA receptor. Among the NMDA receptor antagonists both noncompetitive (e.g., dizocilpine) and competitive antagonists (e.g., CGP 40116) are capable of substituting for ethanol. Further, some antagonists of strychnine-insensitive glycine modulatory sites among the NMDA receptor complex (e.g., L-701,324) dose-dependently substitute for the ethanol discriminative stimulus. On the other hand, neither GABA-benzodiazepine antagonists nor NMDA receptor agonists produce contradictory effects (i.e., reduce the ethanol discriminative stimulus). There is influence of a particular training dose of ethanol on the substitution pattern of different compounds. For example, 5-HT(1B/2C) agonists substitute for intermediate (1.0 g/kg) but not higher (2.0 g/kg) ethanol training doses. Discrimination studies with ethanol and drugs acting on NMDA and GABA receptors consistently indicate asymmetrical generalization. For example, ethanol is able to generalize to barbiturates and benzodiazepines, but neither the benzodiazepine nor barbiturate response generalizes to ethanol. Only a few drugs are able to antagonize, at least to some extent, the discriminative stimulus of ethanol (e.g., partial inverse GABA-benzodiazepine receptor antagonist Ro 15-4513 and the opioid antagonist naloxone). The ethanol stimulus effect may be increased (i.e., stronger recognition) by N-cholinergic drugs (nicotine), dopaminergic drugs (apomorphine), and 5-HT3 receptor agonists (m-chlorophenylbiguanide). Thus, the ethanol stimulus is composed of the several components, with the NMDA receptor and GABA(A) receptor complex being of particular importance. This suggests that a drug mixture may be more capable of substituting for ethanol (or block its stimulus) than a single compound. The ability of drugs to substitute for the ethanol discriminative stimulus is frequently, although not preclusively, associated with the reduction of voluntary ethanol consumption. The examples of positive correlation are gamma-hydroxybutyrate, possibly memantine and certain serotonergic drugs such as fluoxetine. However, it remains uncertain to what extent the discriminative stimulus of ethanol can be seen as relevant in the understanding of the complex mechanisms of dependence.
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PMID:Discriminative stimulus effects of ethanol: neuropharmacological characterization. 989 39

We examined synaptic connectivity between cholinergic and serotonergic neurons in the dorsal raphe nucleus and the laterodorsal tegmental nucleus of the rat. To this purpose we employed two variations (the combination of pre-embedding immunogold-silver intensification with avidin-biotin-peroxidase complex technique and the combination of avidin-biotin-peroxidase/3, 3'-diaminobenzidine/silver-gold intensification with avidin-biotin-peroxidase/3,3'-diaminobenzidine reaction) of a double pre-embedding immunoelectron procedure, using primary antibodies against vesicular acetylcholine transporter and serotonin. At the light-microscopic level, serotonin-like immunoreactive neurons in the dorsal raphe nucleus appeared as reddish black and vesicular acetylcholine transporter-like immunoreactive axon terminals were brown colored using a combination of pre-embedding immunogold-silver technique and avidin-biotin-peroxidase complex technique. Serotonin-like immunoreactive fibers projected to the laterodorsal tegmental nucleus. At the electron microscopy level, with both methods we observed in the dorsal raphe nucleus vesicular acetylcholine transporter-immunopositive axon terminals in synaptic contact with serotonin-like immunoreactive dendrites and, to a lesser degree, with serotonin-like immunoreactive cell bodies. These synapses usually were of the symmetrical type. Occasionally we noted, next to vesicular acetylcholine transporter-immunopositive axon terminals, also immunonegative terminals synapsing with the serotonin-like immunoreactive dendrites. In the laterodorsal tegmental nucleus we found serotonin-like immunoreactive axon terminals and immunonegative terminals forming synapses with vesicular acetylcholine transporter-immunoreactive dendrites. Most synapses formed by the serotonin-like immunopositive terminals were of the asymmetrical type. Our results suggest that serotonergic neurons in the dorsal raphe nucleus and cholinergic neurons in the laterodorsal tegmental nucleus may reciprocally influence each other by means of synaptic connectivity. Such connectivity may serve to regulate pain sensation, or be involved in the regulation of the sleeping-waking cycle.
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PMID:Synaptic contacts between serotonergic and cholinergic neurons in the rat dorsal raphe nucleus and laterodorsal tegmental nucleus. 1082 37

The ultrastructural features of serotonergic fibers, terminals and synaptic contacts were studied with the pre-embedding immunocytochemical method in the isthmo-optic nucleus of the pigeon centrifugal visual system. The 5-HT immunoreactive (-ir) profiles were diffusely distributed and their density was low. The labeled axons were thin and unmyelinated (mean diameter=0.21+/-0.03 microm) though a few larger myelinated axons were observed (mean diameter=0.51+/-0.07 microm). The 5-HT-ir terminals or varicosities were small (diameter=0.71+/-0.54 microm) and contained small agranular synaptic vesicles (diameter=28.5+/-6.9 nm) and large granular vesicles (diameter=102.2+/-19.5 nm). The latter only constituted approximately 1% of the total profiles containing synaptic vesicles in the isthmo-optic nucleus. In single thin sections, only 5% of the 5-HT-ir varicosities exhibited an active asymmetrical zone synapsing upon dendritic profiles of centrifugal visual neurons. Calculations indicated that 17% of these 5-HT-ir varicosities were actually engaged in junctional synaptic relationships, whereas the remaining (83%) were nonjunctional. The data suggest that, within the isthmo-optic nucleus, 5-HT acts both at synaptic junctions (wiring transmission) and at a distance via the extracellular space (volume transmission). These 5-HT afferents could thus modulate the activity of the retinopetal neurons and visual information processing.
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PMID:Serotonergic innervation of the isthmo-optic nucleus of the pigeon centrifugal visual system. An immunocytochemical electron microscopic study. 1174 6

Pre-embedding immunoperoxidase (for serotonin) and postembedding immunogold (for gamma-aminobutyric acid; GABA) labelling were combined at light and electron microscopic levels to demonstrate the neuronal targets of serotonin (5-HT) afferents in the ventral posterior lateral nucleus (VPL) of the cat thalamus. 5-HT-immunoreactive fibres and terminal varicosities were found in close proximity to GABA-immunoreactive interneurons and non-GABAergic relay neurons. Ultrastructurally, the vast majority of 5-HT terminals made close membrane contacts without overt membrane specializations with GABAergic axon terminals, GABAergic presynaptic dendrites and GABAergic somata. A very small number of 5-HT terminals formed typical asymmetrical synapses with GABAergic presynaptic dendrites and with dendritic shafts of relay cells. Some 5-HT terminals participated with the presynaptic dendrites in triadic synaptic arrangements. These findings suggest a dual innervation pattern by 5-HT afferents in VPL and the release of 5-HT in large part at sites not associated with morphologically detectable synapses.
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PMID:Simultaneous Demonstration of Serotonin-immunoreactive Terminals and GABAergic Neurons in the VPL Nucleus of the Cat Thalamus. 1210 12

The main purpose of this light and electron microscopic immunocytochemical study was to characterize and compare the serotonin (5-HT) innervation of the subthalamic nucleus (STN) in rats and squirrel monkeys (Saimiri sciureus) following labeling with an antibody against the 5-HT transporter (SERT). Unbiased counts of SERT+ axon varicosities revealed an average density of 5-HT innervation higher in monkeys (1.52 x 10(6) varicosities/mm3) than rats (1.17 x 10(6)), particularly in the anterior half of the nucleus (1.70 x 10(6)). As measured by electron microscopy, SERT+ axon varicosity profiles in the STN of both species were smaller than unlabeled profiles. The number of SERT+ profiles displaying a synaptic junction indicated that, in both rat and monkey STN, approximately half of 5-HT axon varicosities were asynaptic. In monkeys, all synaptic junctions made by SERT+ varicosities were asymmetrical, as opposed to only 77% in rats. Despite the higher density of 5-HT innervation in the anterior half of monkey STN, the ultrastructural features of its SERT+ varicosities, including synaptic incidence, did not significantly differ from those in its posterior half. These findings suggest that, throughout the rat and monkey STN, 5-HT afferents may exert their influence via both synaptic delivery and diffusion of 5-HT, and that an ambient level of 5-HT maintained in STN by these two modes of transmission might also modulate neuronal activity and influence motor behavior. A better understanding of the factors governing the complex interplay between these signaling processes would greatly improve our knowledge of the physiopathology of the STN.
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PMID:Distribution and ultrastructural features of the serotonin innervation in rat and squirrel monkey subthalamic nucleus. 2034 24

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